What’s new in Hair – June 2018 | Dr. Sergio Vañó-Galván

5-alpha-reductase inhibitor treatment for frontal fibrosing alopecia: an evidence-based treatment update

J Eur Acad Dermatol Venereol. 2018 Mar 10. doi: 10.1111/jdv.14930.
Murad A, Bergfeld W.

Interesting systematic review with the objective of analysing the efficacy and safety of 5-alpha-reductase inhibitors (5ARI) for the treatment of frontal fibrosing alopecia (FFA). The authors perform an evidence-based analysis of the articles published on the use of 5ARI (finasteride and dutasteride) to treat FFA between 2005 and 2017. The level of evidence was graded according to the American College of Physicians outcome study grading system.
Of the total of articles, there were two studies with moderate-level of evidence that described the efficacy of 5ARI for treatment of FFA. 5ARI was commonly used as adjunctive therapy with positive results in recalcitrant disease. Mild-to-moderate hair regrowth was reported in one grade 2 and three lower grade (one grade 3 and two grade 4) studies. There is limited evidence on the safety aspects of this medication in most studies that were analysed.
This review supports the use of finasteride and dutasteride in the treatment of FFA. Although the exact mechanism of action is unknown, patients treated with 5ARI achieved either disease stability or reduction in the rate of progression more frequently than with other therapies. Future randomised, double-blind, controlled studies should be performed to confirm the usefulness of 5ARI in the treatment of FFA.


Endocrine Therapy-Induced Alopecia in Patients With Breast Cancer

JAMA Dermatol. 2018 Apr 11. doi: 10.1001/jamadermatol.2018.0454
Freites-Martinez A, Shapiro J, Chan D, Fornier M, Modi S, Gajria D, Dusza S, Goldfarb S, Lacouture ME.

Endocrine therapy in breast cancer modulates endocrine receptor–mediated pathways. Selective estrogen receptor modulators include tamoxifen, raloxifene, and toremifene, which are competitive inhibitors of estrogen binding to endocrine receptors. By contrast, aromatase inhibitors, including anastrozole, letrozole, and exemestane, suppress plasma estrogen levels by inhibition of aromatase and are now considered the preferred option for adjuvant endocrine therapy in postmenopausal patients. Alopecia in patients receiving endocrine therapy has been anecdotally reported.
In this study, the authors perform a retrospective analysis of the frequency of endocrine therapy-induced alopecia (EIA) in a cohort of 112 patients with breast cancer treated with hormonal therapy (aromatase inhibitors or tamoxifen).
The results were interesting: alopecia was attributed to aromatase inhibitors in 75 patients (67%) and tamoxifen in 37 (33%). Severity was grade 1 in 96 of 104 patients (92%), and the pattern was similar to androgenetic alopecia. The predominant trichoscopic feature at baseline was the presence of vellus hairs and intermediate- and thick-diameter terminal hair shafts. A negative impact on QoL was reported, with a higher effect in the emotion domain according to the Hairdex score (mean [SD], 41.8 [21.3]; P < .001). After treatment with topical minoxidil, moderate or significant improvement in alopecia was observed in 37 of 46 patients (80%).
In conclusion, endocrine therapies are associated with a pattern alopecia similar to androgenetic-type.


Alopecia areata: a review of disease pathogenesis

Br J Dermatol. 2018 May 23. doi: 10.1111/bjd.16808.
Rajabi F, Drake LA, Senna MM, Rezaei N.

Alopecia areata is a non-scarring hair loss with an unpredictable course and a wide spectrum of manifestations. It is an autoimmune phenomenon resulting from disturbances in hair follicle immune privilege. This is mediated through MHC presentation and IFNγ expression. It is already known that polymorphisms in genes related to immune system, structural proteins, and antioxidant enzymes increase susceptibility to alopecia areata.
The main theory of alopecia areata pathogenesis is that it is an autoimmune phenomenon resulting from a disruption in hair follicle immune privilege. What causes this breakdown is an issue of debate. In this interesting article, Rajabi et al review the two main theories of privilege collapse: the stressed hair follicle theory involving MICA expression and the immune system dysregulation hypothesis. The authors also review the contribution of other less identified factors, such as IL-15, T helper-17, mast cells, plasmacytoid dendritic cells, vitamin D receptors, and the neuroendocrine-immune system. Other issue discussed in the article is the AIRE gene and its relevance to alopecia areata.


Peroxisome Proliferator-Activated Receptor-γ-Mediated Signaling Regulates Mitochondrial Energy Metabolism in Human Hair Follicle Epithelium

J Invest Dermatol. 2018 Feb 13. pii: S0022-202X(18)30118-0
Ramot Y, Alam M, Oláh A, Bíró T, Ponce L, Chéret J, Bertolini M, Paus R.

Peroxisome proliferator-activated receptors (PPARs) have many important roles in the regulation of a large number of physiological processes, including cell proliferation, differentiation and inflammatory responses. Agonistic PPARγ modulators may exert protective functions on keratin 15+ epithelial progenitor cells in human hair follicles (HFs), while they inhibit hair growth by inducing catagen and inhibiting the proliferation of hair matrix keratinocytes. Recently, PPARγ-mediated signalling has also been implicated in the regulation of mitochondrial energy metabolism.
In this nice study, Dr. Ramot et al examined whether PPARγ stimulation impacts on the mitochondrial biology of human HF keratinocytes in situ. They analyse if the selective (agonistic) PPARγ modulator, N-Acetyl-GED-0507-34-Levo (N-Acetyl-GED) can modulate mitochondrial properties. N-Acetyl-GED significantly upregulated expressions of all the tested “mitochondrion-relevant” genes (i.e. MTCO1, TFAM, PGC1α, VDAC1 and SLC25A3) in the cells of the investigated donor as compared to the vehicle-treated group. The effects of N-Acetyl-GED were also tested in isolated human outer root sheath (ORS) keratinocytes in culture, and the results of this pilot experiment revealed more prominent actions on “pure” ORS keratinocyte cultures than in intact HFs, inviting the hypothesis that, within the HFs, ORS keratinocytes may be the primary targets of N-Acetyl-GED-mediated PPARγ activation. The results of the study also suggested that PPARγ-mediated signalling is a player in regulating the energy metabolism of human scalp HFs by enhancing mitochondrial function, most probably primarily in the ORS keratinocytes.


An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis

J Invest Dermatol. 2018 Feb 13 pii: S0022-202X(18)30117-9
Jabbari A, Sansaricq F, Cerise J, Chen JC, Bitterman A, Ulerio G, Borbon J, Clynes R, Christiano AM, Mackay-Wiggan J.

Interesting study about one of the hot-topics in trichology: the treatment of alopecia areata with JAK inhibitors. Tofacitinib is a JAK1/3 inhibitor that also inhibits JAK2. Presently, tofacitinib is Food and Drug Administration-approved for the treatment of adult patients with moderate to severe rheumatoid arthritis, psoriatic arthritis and ulcerative colitis, and is under study for many other autoimmune conditions. In this open-label pilot study, Jabbari et al. analyze the efficacy of tofacitinib in moderate-to-severe patchy alopecia areata, alopecia totalis and alopecia universalis. A total of 12 patients were treated with oral tofacitinib 5 mg to 10 mg bid with a clinical response of >50% regrowth in 8 out of 12. The relapse occurred in 7 out of 8 after a median time of 2 months. The safety profile was acceptable in 11 out of 12 patients, with only mild infections. Nevertheless, one patient had to withdraw tofacitinib due to a hypertensive urgency.
In conclusion, the authors stated that the studies of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate to severe AA, providing strong rationale for larger clinical trials using JAK inhibitors in AA.


Microneedling for the treatment of hair loss?

J Eur Acad Dermatol Venereol. 2018 Apr;32(4):564-569
Fertig RM, Gamret AC, Cervantes J, Tosti A.

Microneedling is a minimally invasive dermatological procedure in which fine needles are rolled over the skin to puncture the stratum corneum, inducing collagen formation, neovascularization and growth factor production of treated areas. It is an emerging therapy in androgenetic alopecia (AGA) and other types of alopecia such as alopecia areata. This nice review summarizes the current literature regarding microneedling in the treatment of alopecia.
Microneedling facilitates penetration of first-line medications for hair loss like minoxidil, and this is one mechanism by which it promotes hair growth. To date, the area most studied and with the most success has been microneedling treatment of AGA. After analysing the published studies, the authors state that microneedling shows some promise in improving hair growth, especially in combination with existing techniques.
Regarding alopecia areata, microneedling does not have enough evidence to conclude efficacy; however, the use of needling to improve penetration of topical steroids is of interest and shows the most promise.

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